Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism
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Stephanopoulos_Metformin decreases.pdf
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Author(s)
Fendt, Sarah-Maria
Bell, Eric L.
Keibler, Mark Andrew
Davidson, Shawn Michael
Wirth, Gregory J.
Fiske, Brian Prescott
Mayers, Jared R.
Schwab, Matthias
Bellinger, Gary
Csibi, Alfred
Date Issued
May 2013
Journal
Cancer Research
Publisher
American Association for Cancer Research
Citation
Fendt, S.-M., E. L. Bell, M. A. Keibler, S. M. Davidson, G. J. Wirth, B. Fiske, J. R. Mayers, et al. “Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism.” Cancer Research 73, no. 14 (May 17, 2013): 4429–4438.
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Author's final manuscript
Abstract
Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1158/0008-5472.can-13-0080
